{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:16:21Z","timestamp":1768464981893,"version":"3.49.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFD0501803"],"award-info":[{"award-number":["2018YFD0501803"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>Bovine endometrial stromal cells (bESCs) are exposed to a complex environment of bacteria and viruses due to the rupture of epithelial cells after delivery. Inflammatory responses are elicited by the activation of host pattern recognition receptors through pathogen-related molecules such as lipopolysaccharides (LPS) on the cell membrane. Forsythoside A (FTA) is a major active constituent of <jats:italic>Forsythia suspensa<\/jats:italic> (Thunb.) Vahl. is a flowering plant widely employed as a traditional Chinese herbal medicine to treat various inflammatory diseases such as nephritis, eye swelling, scabies, ulcers, and mastitis; however, the molecular mechanisms underlying its therapeutic effects on bovine endometritis are still unclear. The aim of this study was to explore the role of miRNA and the mechanisms underlying the protective activity of FTA on the inflammation of bovine endometrial stromal cells induced by LPS. Based on previous research, we isolated and cultured bESCs <jats:italic>in vitro<\/jats:italic> and categorized them into LPS and LPS+FTA groups with three replicates. Upon reaching 80% confluence, the bESCs were treated with 0.5 \u03bcg\/mL of LPS or 0.5 \u03bcg\/mL of LPS + 100 \u03bcg\/mL of FTA. We, then, performed high-throughput sequencing (RNA-Seq) to investigate the effects of FTA on LPS-stimulated primary bESCs and their underlying mechanisms. We identified 167 miRNAs differentially expressed in the LPS groups; 72 miRNAs were up-regulated, and 95 were down-regulated. Gene ontology enrichment analysis revealed that differentially expressed microRNA (DEGs) were most enriched during the cellular metabolic process; they were mostly located intracellularly and participated in protein, enzyme, and ion binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were most enriched in the mitogen-activated protein kinase, tumor necrosis factor, and Interleukin-17 signaling pathways. These results reveal the complex molecular mechanism involved in the FTA and provide a basis for future studies of bovine endometritis treatment with traditional Chinese medicine monomer.<\/jats:p>","DOI":"10.3389\/fvets.2021.642913","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T06:07:20Z","timestamp":1614146840000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Role of MicroRNAs in Protective Effects of Forsythoside A Against Lipopolysaccharide-Induced Inflammation in Bovine Endometrial Stromal Cells"],"prefix":"10.3389","volume":"8","author":[{"given":"Haimiao","family":"Lv","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenbo","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lixin","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhan","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dexin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjv","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuefen","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Tong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinzhuang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1516","DOI":"10.1016\/j.theriogenology.2005.08.021","article-title":"Defining postpartum uterine disease in cattle","volume":"65","author":"Sheldon","year":"2006","journal-title":"Theriogenology."},{"key":"B2","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s13028-016-0257-9","article-title":"A longitudinal cohort study of acute puerperal metritis cases in Swedish dairy cows","volume":"58","author":"Ordell","year":"2016","journal-title":"Acta Vet Scand."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1095\/biolreprod.109.077370","article-title":"Defining postpartum uterine disease and the mechanisms of infection and immunity in the female reproductive tract in cattle","volume":"81","author":"Sheldon","year":"2009","journal-title":"Biol Reprod."},{"key":"B4","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.theriogenology","article-title":"Preventing postpartum uterine disease in dairy cattle depends on avoiding, tolerating and resisting pathogenic bacteria","volume":"150","author":"Sheldon","year":"2020","journal-title":"Theriogenology."},{"key":"B5","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1095\/biolreprod.111.092718","article-title":"Toll-like receptor 4 and MYD88-dependent signaling mechanisms of the innate immune system are essential for the response to lipopolysaccharide by epithelial and stromal cells of the bovine endometrium","volume":"86","author":"Cronin","year":"2012","journal-title":"Biol Reprod."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1210\/en.2013-1822","article-title":"Epithelial and stromal cells of bovine endometrium have roles in innate immunity and initiate inflammatory responses to bacterial lipopeptides in vitro via Toll-like receptors TLR2, TLR1, and TLR6","volume":"155","author":"Turner","year":"2014","journal-title":"Endocrinology."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1016\/j.theriogenology.2009.01.006","article-title":"Histopathological and molecular evaluation of Holstein-Friesian cows postpartum: toward an improved understanding of uterine innate immunity","volume":"71","author":"Chapwanya","year":"2009","journal-title":"Theriogenology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1530\/jrf.0.0180493","article-title":"Reproductive physiology of the postpartum cow. 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